Iberdomide
Zenbexus · Cereblon E3 ligase modulator (CELMoD)
2026 first-in-class CELMoD; no attributable lesion (renal impairment 11% vs 8% on the comparator arm) but exposure rises 1.8x below eGFR 30 off dialysis.
PRE
Mild#1 · 89% phenotype match
Zidesamtinib
Jideytro · ZDS
ROS1-selective TKI · approved 2026 · 4 citations
Up to date· through 2026
Thinly sourced3/9 · 3 signals
- Not met: 4 citations
- Not met: 12+ references
- Not met: Accrued over 10+ years (span: 1y)
- Met: Beyond single case reports
- Not met: Peer-reviewed sources
- Met: Landmark reference
- Met: Current through 2026
- Not met: Real-world FAERS signal
Describes how this page is sourced, not how dangerous the drug is. Thinly sourced means fewer of the sourcing signals are met — not that the agent is kidney-safe. A rule-based summary, not a formal certainty appraisal.
A ROS1-selective, TRK-sparing TKI whose kidney story is a teachable negative: no creatinine abnormality reached its label's >=20% laboratory-table cutoff — unlike the benign creatinine rise that runs through the rest of its class.
MildROS1-selective (TRK-sparing) TKI
Locally advanced or metastatic ROS1-positive non-small-cell lung cancer in adults who received a prior ROS1 kinase inhibitor (ARROS-1)Under study in TKI-naive ROS1-positive NSCLC and other ROS1-positive solid tumors (ARROS-1 phase 2 cohorts)
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Signature kidney injury
Signature lesion
No drug-specific renal adverse-event incidence is published, and — notably for this class — creatinine increase does not appear in the FDA label's laboratory-abnormality table — which tabulates only abnormalities that worsened in >=20% of patients — nor in its >=2% grade 3-4 summary, so the absence establishes a rate below those cutoffs, not zero. The most common adverse reactions on the label's pooled safety population are edema (38%), peripheral neuropathy (25%), constipation (17%), fatigue (16%) and dyspnea (15%); the tabulated laboratory abnormalities are led by increased cholesterol and triglycerides (47% each) and increased CPK (37%), with decreased hemoglobin (30%), increased amylase (23%) and increased alkaline phosphatase (21%) further down the table. This absence of a creatinine signal is consistent with the drug's selective design but rests on early registrational data — it is an observation about what the label reports, not proof of renal inertness.Source: No drug-specific renal incidence; no creatinine abnormality reached the label's >=20% lab-table cutoff — common ARs are edema 38%, peripheral neuropathy 25%, constipation 17% (pooled label safety population)
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Renal toxicities, ranked
This agent's defining kidney lesion — its #1 signature. Cited incidence is shown where a citable figure exists; otherwise the tier stands qualitatively.
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.
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Kidney injury
Mechanism of kidney injury
No direct renal toxicity is established. The class context is the reason the kidney question comes up at all: crizotinib, entrectinib, repotrectinib and taletrectinib — the catalog's other ROS1 inhibitors — carry a benign, transporter-mediated creatinine rise (inhibited tubular creatinine secretion reading as pseudo-AKI), and crizotinib adds renal cysts. Zidesamtinib's label lists neither, which fits its deliberately narrowed kinase footprint, though a transporter interaction that registrational tables missed cannot be excluded this early. What remains is indirect and generic: fluid retention (edema in 38%) reflects drug-related fluid handling rather than a nephrotic process, and any creatinine rise would most plausibly be prerenal from an intercurrent illness rather than an intrinsic lesion.
Clinical presentation
No characteristic renal presentation is expected. Peripheral edema is the finding most likely to raise a kidney question — on this drug it is a class fluid-retention effect, not a renal sign, and it should not be equated with nephrotic syndrome without checking urine protein. A creatinine rise warrants the standard prerenal-versus-intrinsic workup with attention to other causes, because the label gives no basis for attributing it to zidesamtinib.
Management
No zidesamtinib-specific renal management exists. Manage edema symptomatically and confirm it is not renal (urine protein, albumin) before treating it as such. A prerenal creatinine rise responds to volume restoration and treating the precipitant. Because the label documents no creatinine effect for this drug, a significant creatinine rise should trigger a genuine workup — volume, obstruction, other drugs, disease — rather than the 'benign TKI creatinine rise' shrug its class siblings have earned; that shortcut has no evidence base here.Lesion-level management framework
Risk factors
- Intercurrent volume depletion (poor intake, vomiting, diarrhea) producing prerenal physiology
- Baseline CKD — the label recommends no dosage modification for eGFR 30-90 mL/min but the effect of eGFR <30 or dialysis is unknown
- Concurrent nephrotoxins or contrast, which the drug itself does nothing to protect against
- Significant edema complicating volume assessment
Prevention
- Complete the label's pre-initiation evaluation — CPK, electrolytes, ECG, lipase and amylase — before the first dose, and correct abnormalities it surfaces
- Maintain hydration during intercurrent GI illness
Anticancer mechanism· how it treats cancer
Oral, brain-penetrant macrocyclic tyrosine kinase inhibitor designed for selective ROS1 inhibition while sparing tropomyosin-receptor kinases (TRK). It maintains potency against the resistance mutations that defeat earlier agents — including the solvent-front ROS1 G2032R — and its TRK-sparing design removes the off-target neurologic toxicity that limited prior ROS1/TRK inhibitors. Approved on the ARROS-1 program for ROS1 fusion-positive non-small-cell lung cancer previously treated with a ROS1 kinase inhibitor.
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Clinical depth
Renal dose adjustment
No dosage modification is recommended for eGFR 30-90 mL/min; the label states the effect of severe renal impairment (eGFR <30 mL/min) or dialysis on zidesamtinib pharmacokinetics is unknown. Dose changes are driven by the drug's own toxicities (CPK elevation with myalgia, pancreatic enzyme elevation, QT), not by kidney function.
Dialyzability & ESKD dosing
Not characterized: the label explicitly lists the effect of dialysis on zidesamtinib pharmacokinetics as unknown. As an orally dosed, metabolically cleared kinase inhibitor it is unlikely to be meaningfully dialyzable, and no drug-removal scenario applies.
Differential diagnosis
The class trap runs in reverse here. For crizotinib or taletrectinib, a modest creatinine rise is usually the benign transporter effect; zidesamtinib's label documents no such effect, so the same lab finding on this drug deserves a real workup — prerenal physiology, obstruction, another nephrotoxin, or disease — instead of class-based reassurance. Separate drug-related peripheral edema (common, bland urine, normal albumin) from a nephrotic process before attributing fluid to the kidney.
Monitoring
- Routine serum creatinine as part of standard oncologic care — with the knowledge that a rise is NOT an expected drug effect on this agent
- Urine protein if edema is generalized or out of proportion, to separate fluid retention from a renal process
- CPK, electrolytes, lipase and amylase per the label's schedule (the drug's actual laboratory toxicities)
- Volume status during intercurrent illness
Key trials & series
- ARROS-1 (phase I/II; label efficacy population N=117, all ROS1-TKI-pretreated) — registrational study behind the prior-TKI indication: confirmed ORR 44% overall (95% CI 34-53), 49% after one prior ROS1 TKI, 38% after two or more. The earlier ESMO 2024 data cut (van der Wel, Lung Cancer 2025) reported 73% in a crizotinib-pretreated subgroup — a subgroup figure from an interim cut, not the approved-population rate.
- AURORA-ROS1 registry (Itchins, Lung Cancer 2026) — Australian multicentre real-world cohort in which zidesamtinib appears among later-generation first-line ROS1 inhibitors (median PFS 48 months for the later-generation group) — early real-world context, no renal signal reported.
Clinical pearls
- The teachable point is the absence: every other ROS1 TKI in this atlas raises creatinine benignly; on zidesamtinib's label no creatinine abnormality reached the >=20% laboratory-table cutoff — selectivity with a visible kidney consequence.
- Do not import the class's 'benign creatinine rise' reassurance — on this drug that shortcut has no evidence base, so work a real rise up properly.
- Edema in 38% is fluid retention, not nephrosis — check urine protein before blaming the kidney.
- No dose change down to eGFR 30; below that (and on dialysis) the pharmacokinetics are simply unknown.
- Its label-warned laboratory toxicities are CPK, lipase and amylase — the baseline panel the label mandates is the monitoring that matters; the lipid elevations (cholesterol and triglycerides, 47% each) are the most frequent lab abnormalities but carry no label warning.
Where it strikes· nephron segments & injury signatures
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
Injury signatures
Beyond the kidney — non-renal toxicities· 3 organ systems
Class-level context for the major non-renal toxicities of the ROS1-selective TKI class.
Ophthalmic
Keratopathy, uveitis, retinopathy
- Visual disturbance (crizotinib)
Hepatic / Liver
Transaminitis, hepatitis, VOD/SOS
- Transaminitis
Neurologic
Neuropathy, encephalopathy, ICANS, PRES
- CNS effects (lorlatinib)
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References
4 primary references — trials, cohorts, mechanism, and reviews. Citation metadata via PubMed / NLM.
Evidence accrual
4 references · 2025–2026 · 4 since 2024Primary (non–case-report) references per year — a proxy for how actively the agent's renal literature is accruing. Recent years are highlighted. Reflects curation depth, not a systematic bibliometric count.
- 1.LandmarkNovel strategies for rare oncogenic drivers in non-small-cell lung cancer: An update from the 2024 Annual ESMO meeting.van der Wel JWT, de Langen AJ · Lung Cancer · 2025 · PMID 40118657Carries the ESMO 2024 ARROS-1 interim results for zidesamtinib, a ROS1-selective and TRK-sparing TKI: ORR 73% in a crizotinib-pretreated subgroup and 38% after repotrectinib. The label's registrational figures for the approved prior-TKI population are lower — confirmed ORR 44% overall (N=117) — so the abstract's subgroup rates should be read as such.
- 2.Zidesamtinib Selective Targeting of Diverse ROS1 Drug-Resistant Mutations.Tangpeerachaikul A, Mente S, Magrino J, et al. · Mol Cancer Ther · 2025 · PMID 40299789The design paper: ROS1-selective macrocycle inhibiting >1,500 pooled ROS1 mutants (including G2032R) while structurally avoiding TRK — the selectivity that underlies both its neurologic tolerability and the absence of the class's off-target laboratory effects.
- 3.Targeting ROS1 rearrangements in non-small cell lung cancer: Current insights and future directions.Desilets A, Repetto M, Yang SR, Drilon A · Cancer · 2025 · PMID 40171848Class landscape review situating zidesamtinib as the highly selective next-generation agent that addresses TRK-mediated off-target toxicities of prior ROS1 inhibitors — the context for reading its safety profile against crizotinib-era expectations.
- 4.Real-world treatment sequencing and survival in ROS1-Rearranged NSCLC across evolving treatment eras: Findings from the AURORA multi-centre registry (AURORA-ROS1).Itchins M, Alexander M, Kao S, et al. · Lung Cancer · 2026 · PMID 42365776Multicentre real-world registry in which zidesamtinib appears among later-generation first-line ROS1 inhibitors (median PFS 48 months for that group) — early real-world usage context with no renal signal reported.
FDA label — boxed warning & renal dosing· renal impairment
Quoted verbatim from this agent's current FDA label (Jul 2026) — not paraphrased or interpreted. Full label on DailyMed .
Renal impairment — from the label
The effect of severe renal impairment (eGFR <30 mL/min) or dialysis on zidesamtinib pharmacokinetics is unknown. No dosage modification is recommended for patients with eGFR 30 to 90 mL/min [see Clinical Pharmacology ( 12.3 )] .
Guidelines & consensus· 13
Each recommendation below is this atlas's faithful summary of the source, not a quotation from it — follow the PubMed link for the wording the society published. Summaries may be superseded; consult the current full text and individualize to the patient.
General onco-nephrology references
ADQIThe nephrotoxic effects of anti-cancer therapies: consensus report of the 34th Acute Disease Quality Initiative workgroupNat Rev Nephrol 2026 · PMID 41361704Provides expert-based statements (modified Delphi) on preventing and managing cisplatin/platinum-associated AKI, including isotonic IV hydration, attention to volume status and concomitant nephrotoxins, and incorporates evidence that IV magnesium supplementation may reduce cisplatin-associated AKI; emphasizes risk stratification and standardized AKI definitions.SIRMSIRM-SIN-AIOM: appropriateness criteria for evaluation and prevention of renal damage in the patient undergoing contrast medium examinations-consensus statements from Italian College of Radiology (SIRM), Italian College of Nephrology (SIN) and Italian Association of Medical Oncology (AIOM)Radiol Med 2022 · PMID 35303246Recommends eGFR-based renal risk assessment and pre/post-contrast isotonic saline or sodium bicarbonate hydration; advises maintaining a 5-7 day interval between iodinated contrast administration and cisplatin in cancer patients to reduce additive nephrotoxicity.KDIGOKDIGO Controversies Conference on onco-nephrology: understanding kidney impairment and solid-organ malignancies, and managing kidney cancerKidney Int 2020 · PMID 33126977Identifies platinum compounds (especially cisplatin) as leading cytotoxic causes of acute tubular injury, AKI, and electrolyte/magnesium wasting; calls for interdisciplinary onco-nephrology care, accurate GFR estimation, and individualized drug dosing in patients with reduced kidney function.KDIGOKDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantationKidney Int 2020 · PMID 33276867Addresses chemotherapy-associated AKI/CKD in hematologic cancer, GFR estimation and chemotherapy dosing in patients with reduced kidney function, and management priorities and research gaps for onco-nephrology care.ADDIKDIntegrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practiceEClinicalMedicine 2025 · PMID 40290844Provides GRADE-based, drug-specific dose-adjustment recommendations for anticancer agents in kidney dysfunction (illustrated for methotrexate, cisplatin, carboplatin and nivolumab); the recommendations build on Part 1's standardised CKD-EPI eGFR assessment rather than Cockcroft-Gault creatinine clearance.ADDIKDAligning kidney function assessment in patients with cancer to global practices in internal medicineEClinicalMedicine 2025 · PMID 40290845Three consensus recommendations: assess kidney function by GFR (measured GFR or CKD-EPI eGFR), classify it using KDIGO categories, and use this uniform approach to dose anticancer drugs — moving cancer medicine away from Cockcroft-Gault estimated creatinine clearance.ADDIKDA methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney functionEClinicalMedicine 2025 · PMID 40290846Establishes that, where RCT evidence is lacking, anticancer drug dosing recommendations in kidney dysfunction should be derived by critically appraising observational literature via GRADE combined with structured international multidisciplinary consensus voting.KDIGODiagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1)Crit Care 2013 · PMID 23394211Defines/stages AKI by serum creatinine and urine output; emphasizes avoiding nephrotoxins, maintaining euvolemia/perfusion, dose-adjusting drugs to kidney function, and monitoring high-risk patients — the framework applied to nephrotoxic anti-cancer agents.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknownsKidney Int 2024 · PMID 38519239Evaluate and risk-stratify CKD, manage to delay progression and its complications, and practise explicit medication management and drug stewardship — the framework the atlas's G1–G5 eGFR banding and every renal dose-adjustment recommendation sit inside. Because the guideline excludes dialysis and transplant recipients by its own statement of scope, its recommendations do not carry to those settings, where this atlas's dialyzability and post-transplant guidance rests on other sources.KDIGOExecutive summary of the KDIGO 2021 Guideline for the Management of Glomerular DiseasesKidney Int 2021 · PMID 34556300Provides the staging/treatment framework for drug-associated glomerular lesions (e.g., bisphosphonate- and interferon-related collapsing FSGS, VEGF-inhibitor podocytopathy/proteinuria), including immunosuppression and supportive RAAS-blockade strategies.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated VasculitisKidney Int 2024 · PMID 38388147Updates immunosuppressive induction (rituximab/cyclophosphamide), incorporates avacopan and lower-dose or glucocorticoid-sparing regimens — the management framework for drug- and checkpoint-inhibitor-associated ANCA/pauci-immune glomerulonephritis.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus NephritisKidney Int 2024 · PMID 38182299Updates first-line lupus nephritis therapy to combination immunosuppression with the addition of belimumab or a calcineurin inhibitor (voclosporin) — informs management of immune-complex/lupus-like glomerulonephritis encountered with immunotherapy.KDIGOExecutive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV)Kidney Int 2025 · PMID 40975525Encourages liberal kidney biopsy and stricter proteinuria control (<0.5 g/d, ideally <0.3 g/d) with RAAS blockers, SGLT2 inhibitors, and targeted-release budesonide — the framework for IgA-dominant glomerular lesions, including those triggered by immune-modulating cancer therapy.
Where Zidesamtinib sits in nephrotoxicity space — each dot is an anti-cancer agent, positioned so neighbors share a kidney-injury phenotype. Its 6 closest are filled and lead to a numbered marker, matching the numbered cards below.
Phenotype-similar agents· the numbered markers on the map above
Profile
Vepdegestrant
Veppanu · PROTAC estrogen-receptor degrader
2026 first PROTAC ER degrader; no meaningful intrinsic renal signal.
PRE
Mild#2 · 89% phenotype match
Casdatifan
HIF-2α inhibitor (investigational)
Trial-stage RCC HIF-2α inhibitor; renal profile being defined.
PRE
Mild#3 · 89% phenotype match
Dordaviprone
Modeyso · Imipridone (ONC201; DRD2/ClpP)
2025 imipridone for H3 K27M glioma; renally well tolerated — QT prolongation, not nephrotoxicity, is the safety focus.
PRE
Mild#4 · 89% phenotype match
Tovorafenib
Ojemda · Type II pan-RAF (BRAF) inhibitor
2024 pediatric glioma RAF inhibitor; creatinine rise.
PRE
Mild#5 · 89% phenotype match
Elacestrant
Orserdu · Oral selective estrogen-receptor degrader (SERD)
2023 oral SERD; nausea-dominant, minimal intrinsic nephrotoxicity.
PRE
Mild#6 · 89% phenotype match
Nearest agents by kidney-injury phenotype (shared injuries, nephron target, severity, class) — a similarity approximation, not a claim of shared drug identity or mechanism.
Kidney risk across ALK / ROS1 / MET / TRK inhibitors
Same-class agents ordered by their documented kidney-injury profile — atlas severity, an acute-kidney-injury FAERS signal, and how many injury types each is documented to cause. Agents nearer the top carry the lighter documented renal profile.
- 1LarotrectinibPSEUDO — Pseudo-AKIMild
- 2RepotrectinibPSEUDO — Pseudo-AKIMild
- 3TaletrectinibPSEUDO — Pseudo-AKIMild
- 4Zidesamtinib· this agentPRE — Prerenal / Hemodynamic AKIMild
- 5AlectinibPSEUDO — Pseudo-AKIMild
- 6CapmatinibPSEUDO — Pseudo-AKIMild
- 7CeritinibPRE — Prerenal / Hemodynamic AKIMild
- 8TepotinibPSEUDO — Pseudo-AKIMild
- 9BrigatinibPSEUDO — Pseudo-AKIMild
- 10CrizotinibRCYST — Renal CystsMild
- 11EnsartinibPSEUDO — Pseudo-AKIMild
- 12LorlatinibPSEUDO — Pseudo-AKIMild
- 13EntrectinibPSEUDO — Pseudo-AKIFAERS AKIMild
A comparison of documented kidney-injury data within one drug class — not a substitution recommendation. Efficacy, indication, and non-renal toxicity differ between these agents and are out of scope here. Educational only, not medical advice.